January 20-22, 2012 Des Moines Marrio, 700 Grand Avenue, Des Moines, IA Session 4: New Evidence-Based Clinical Prac ce Guidelines B: Management of Osteoporosis in Post-Menopausal Women 4:15pm - 5:15pm ACPE UAN 107-000-12-024-L01-P Ac vity Type: Applica on-based 0.1 CEU/1.0 Hr Program Objec ves for Pharmacists: Upon comple on of this CPE ac vity par cipants should be able to: 1. Iden fy which pa ents will benefit from addi onal calcium supplementa on 2. Recommend a dose of calcium for those pa ents that need supplementa on 3. Recall recommenda ons for vitamin D supplementa on 4. Iden fy common and serious adverse effects associated with long term use of bisphosphonates 5. Recognize those pa ents that would benefit from therapy with recombinant parathyroid hormone therapy Speaker: Ann M. Philbrick, PharmD, BCPS, is an Assistant Professor in the College of Pharmacy at the University of Minnesota and a Clinical Pharmacist at the University of Minnesota Veterinary Medical Center. She is on the faculty of St. Joseph s Family Medicine Residency Program and maintains her pharmacy prac ce at Bethesda Family Medicine Clinic. She is a 2006 graduate of the University of Nebraska Medical Center and completed the combined PGY1 and PGY2 Ambulatory Care Residency at the University of Iowa Hospitals and Clinics in 2008. Dr. Philbrick s prac ce and scholarship interests revolve around the role of a clinical pharmacist within a family medicine clinic. Speaker Disclosure: Ann Philbrick does not report any actual or poten al conflicts of interest in rela on to this CPE ac vity. Off-label use of medica ons will not be discussed during this presenta on.
Management of Osteoporosis in Post-Menopausal Women Ann M. Philbrick, Pharm.D., BCPS Assistant Professor University of Minnesota College of Pharmacy Faculty Disclosure Dr. Philbrick reports she has no actual or potential conflicts of interest associated with this presentation. Dr. Philbrick has indicated that off-label use of medication will not be discussed during this presentation. Learning Objectives Upon completion of this activity pharmacists (or pharmacy technicians) will be able to: Identify which patients will benefit from additional calcium supplementation. Recommend a dose of calcium for those patients that need supplementation. Recall recommendations for vitamin D supplementation. Identify common and serious adverse effects associated with long term use of bisphosphonates. Recognize those patients that would benefit from therapy with recombinant parathyroid hormone therapy. Pre-Assessment Questions 1. Which of the following defines osteoporosis? A. T-Score -1 to -2.5 B. T-Score < -2.5 C. Z-Score -1 to -2.5 D. Z-Score < -2.5 2. What is the drug of choice for treatment of osteoporosis? A. Bisphosphonate B. Teriparatide C. Calcitonin D. All of the Above Pre-Assessment Questions 3. Based on recent studies, how much elemental calcium does a postmenopausal woman, who is getting 750mg of dietary calcium need? A. None B. 250mg C. 450mg D. 1200mg Osteoporosis A Definition Low bone mass Deterioration of the bone tissue / architecture Compromised bone strength Increased risk of fracture Diagnosed by: BMD -2.5 SD at the hip or spine 1
Epidemiology 10 million Americans with Osteoporosis 33.6 million have low bone density* 1 in 2 Caucasian women will experience an osteoporotic fracture in their lifetime Pathophysiology BONE RESORPTION BONE FORMATION Pathophysiology Patient Case Ilene Dover (I.D.) 65 y.o. postmenopausal caucasian woman PMHx: hypertension and asthma. Meds: metoprolol, aspirin, fluticasone and albuterol inhalers SHX: Retired. Married. Tobacco: none. Alcohol: 1 glass of wine daily. Exercise: rides bicycle 4 days per week. ROS : chronic, mild back pain over past 2 years. Vitals: Ht: 66 inches (168 cm) BMI = 24.3 Wt: 150 lbs (68.2 kg) BP 138/60 Family Hx: mom had hip fracture at age 72 Fracture Hx: patient slipped on the ice and fracture wrist 2 years ago. Is I.D. at risk for a fracture? How to Measure Bone Density Central DEXA: images the hip and spine. Used to define osteoporosis, predict risk of fracture, and monitor treatment. Peripheral DEXA: images the forearm, finger, or heel. Predicts fracture risk but not useful for monitoring. CT and Ultrasound based bone density measures are not used at this time. 2
What is a DEXA Scan? DEXA is Dual-energy x-ray absorptiometry Values: T-score Compares bone density to young adults of the same gender. Z-score Compares bone density to age-matched adults of the same gender. Results expressed in standard deviation from the mean. A single standard deviation decline in DXA score predicts a 2.6 relative risk increase in hip fracture. Who Needs a DEXA Scan? Women age 65 and older and men age 70 and older, regardless of clinical risk factors Women in the menopausal transition if there is a specific risk factor associated with increased fracture risk such as low body weight, prior low-trauma fracture, or high risk medication. Younger postmenopausal women and men age 50-70 about whom you have concern based on their clinical risk factor profile Adults who have a fracture after age 50 Who Needs a DEXA Scan? Adults with a condition (e.g., rheumatoid arthritis) or taking a medication (eg glucocorticoids, 5 mg/day for 3 months) associated with low bone mass or bone loss Anyone being considered for pharmacologic therapy for osteoporosis Anyone being treated for osteoporosis, to monitor treatment effect Anyone not receiving therapy in whom evidence of bone loss would lead to treatment Postmenopausal women discontinuing estrogen should be considered for bone density testing. Does I.D. Need a DEXA Scan? YES Why: female & over age 65 year Her Results: -2.0 at the left femoral neck She does NOT have osteoporosis Influence of Age & T-Score on Fracture Rates Risk of Fracture Osteoporos Int. 2006:17:565 NEJM. 2008;358:1474. 3
FRAX Score Fracture Risk Assessment Tool WHO web based fracture risk tool. Input individual Risk Factors for fracture. Gives 10 year fracture rate for both major osteoporotic fractures and hip fractures. High risk is defined as Risk of any fracture > 20% Risk of hip fracture > 3% Key point: FRAX helps us to turn relative risk into absolute risk for individual patients FRAX Score for I.D. Available: http://www.shef.ac.uk/frax/ FRAX Score for I.D. Question: What is I.D. s Risk? HIGH Risk for: Major Osteoporotic Fracture Hip Fracture I.D. should be treated as if she has osteoporosis Does I.D. Need Calcium Supplementation? Adequate Calcium Intake Women older than 50 years: 1200 mg elemental calcium / day National Osteoporosis Foundation 4
Daily Calcium Estimation STEP 1 Product Servings/Day X Estimated elemental = Calcium (mg) calcium/serving (mg) Milk (8oz.) X 300 = Yogurt (6 oz) X 300 = Cheese (1 oz.) X 200 = Fortified foods/juice X 80-1000 = STEP 2: + 250mg from non-dairy sources 250mg TOTAL DAILY CALCIUM INTAKE Daily Calcium Estimation for I.D. STEP 1 Product Servings/Day X Estimated elemental = Calcium (mg) calcium/serving (mg) Milk (8oz.) 1 X 300 = 300 Yogurt (6 oz) 0 X 300 = 0 Cheese (1 oz.) 1 X 200 = 200 Fortified foods/juice 0 X 80-1000 = 0 STEP 2: + 250mg from non-dairy sources 250mg TOTAL DAILY CALCIUM INTAKE 750mg WHI Calcium & CV Risk Re-analysis of Women s Health Initiative CaD Study Original: randomized to receive calcium carbonate 500 mg with vitamin D 200 IU BID or placebo Problem: high personal use of calcium clouded the results New analysis: stratified into two groups personal vs. nonpersonal use of calcium (± vitamin D) WHI Calcium & CV Risk BMJ. 2011;342:2040 BMJ. 2011;342:2040 WHI Calcium & CV Risk Does I.D. Need Calcium Supplementation? Approximate dietary intake: 750mg At this time, no Could recommend more dietary intake Conclusion When persons with no personal calcium supplementation were randomized to receive calcium, they had a high incidence of MI & stroke BMJ. 2011;342:2040 5
Does I.D. Need Vitamin D Supplementation? Screening for Vitamin D Deficiency Screening should be completed in persons at risk for deficiency Rickets Older adults with a hx of falls Osteomalacia Older adults with a hx of nontraumatic fractures Osteoporosis CKD Granuloma-forming disorders Malaborption disorders On certain medications: Hyperparathyroidism Anti-seizure African American person Glucocorticoids Anti-retrovirals Hispanic persons Antifungals Pregnant/Lactating Women Cholestyramine Obese persons J Clin Endocrinol Metab. 2011:96:1911 25-hydroxyvitamin D [25(OH)D] Levels Normal: > 30 ng/ml Insufficiency: 20 30 ng/ml Deficiency: < 20 ng/ml Vitamin D Intake Adequate daily intake 800 1000 IU / day Treatment on deficiency 50,000 IU once weekly or 6,000 IU daily for 8 weeks Maintenance dose: 1500 2000 IU daily J Clin Endocrinol Metab. 2011:96:1911 J Clin Endocrinol Metab. 2011:96:1911 Vitamin D 2 vs D 3 Vitamin D 2 Ergocalciferol Body gets from the food Exception: oil-rich fish Converted to D 3 in the body Vitamin D 3 Cholecalciferol Body gets from sun Readily used by the body Other Uses for Vitamin D Should be prescribed for: Fall prevention Should not be prescribed for: Cardiovascular disease prevention Quality of Life Improvement Guidelines Give No Preference to Either Supplement J Clin Endocrinol Metab. 2011:96:1911 J Clin Endocrinol Metab. 2011:96:1911 6
Does I.D. Need Vitamin D Supplementation? 25(OH)D Level: 31.2 ng/ml Yes 800 1000 IU / day D 2 or D 3 What Pharmacotherapy Should I.D. Receive? Pharmacotherapy Indications Men or women over 50 with hip or vertebral (clinical or morphometric) fracture Prior fractures associated with low bone mass (T-score -1.0 to -2.5) T-score -2.5 or less Low bone mass and glucocorticoid use or need for prolonged immobilization Low bone mass and 10-yr hip fracture rate >3% or 10-yr major osteoporotic fracture risk > 20% based on WHO algorithm Pharmacotherapy Options Bisphonphonates: drugs of choice Parathyroid hormone Calcitonin Bisphosphonates Work by: inhibiting osteoclastic activity Products: Alendronate (Fosamax ) Oral: daily, weekly Risedronate (Actonel, Atelvia ) Oral: daily, weekly, monthly Ibandronate (Boniva ) Oral: daily, monthly Every 3 month infusion Zolendronic Acid (ZA) (Reclast ) Yearly infusion Bisphosphonates Adverse Effects: Gastrointestinal effects Difficulty swallowing, esophageal inflammation, gastric ulcer Osteonecrosis of the jaw Atrial fibrillation with ZA administration Atypical fractures Subtrochanteric & diaphyseal femur fractures Not yet known if related, but most cases have appeared in patients on bisphosphonates Esophageal cancer? FDA statement: benefits of bisphosphonates outweigh the small (possible) risk of cancer 7
Post-Menopausal Osteoporosis ZA vs. placebo in post-menopausal women with osteoporosis Infused at baseline, 12 & 24 months Also received daily calcium/d supplementation Primary Outcome: new vertebral fractures and hip fractures Recurrent Fractures Zolendronic acid (ZA) vs. placebo following surgical repair of hip fracture Primary outcome: New clinical fracture ZA administered within 90 days of fracture Every 12 months thereafter All subjects received loading dose of Vitamin D2 or D3 if deficient All subjects received oral calcium/d vitamin supplementation NEJM; 2007;356:1809 NEJM. 2007;357:1799. Recurrent Fractures Teriparatide (Forteo ) Parathyroid hormone Anabolic effect on bone Given 20 mcg SQ daily Long term safety (>2 years) unknown Increase risk of osteosarcoma in rats One case in humans NEJM. 2007;357:1799. Postmenopausal Women Randomized, double-blind, placebo-controlled trial Teriparatide 20mcg, 40mcg or placebo for 24 months Postmenopausal Women NEJM. 2001;344:1434 NEJM. 2001;344:1434 8
Teriparatide, Alendronate or Both in Post-Menopausal Women Randomized, controlled trial Not placebo controlled Alendronate 10mg daily (group 1), teriparatide 40mcg daily (group 2) or both (group 3) Calcitonin Nasal spray used daily Indicated for post-menopausal osteoporosis May reduce pain associated with fractures J Clin Endocrinol Metab. 2010;95:1838 Postmenopausal Osteoporosis Randomized, double-blind, placebo controlled trial Intranasal calcium daily, TIW or placebo Summary I.D. Needed a DEXA scan based on age, menopausal status DEXA 2.0 low bone density FRAX Scores 32% 10-year risk of major osteoporotic fracture 4.3% 10-year risk of hip fracture Does not need calcium supplementation Does need vitamin D supplementation Would suggest bisphosphonate as first line therapy Not osteoporotic, but is warranted based on high FRAX score CalcifTissue Int. 1996:59:6. Summary BMD does not necessarily confer with fracture risk led to the development of the FRAX Score Current medical theory is straying away from calcium supplementation; encouraging increased dietary intake Vitamin D supplementation Recommended for all at 800 to 1000 IU daily 50,000 IU once weekly for 8 weeks Drug therapy is recommended for T-Score <-2.5, 10-year major osteoporotic fracture risk > 20% or hip fracture risk > 3% Bisphosphonates remain the drug of choice but teriparatide and calcitonin show promise Post-Assessment Questions 1. Which of the following defines osteoporosis? A. T-Score -1 to -2.5 B. T-Score < -2.5 C. Z-Score -1 to -2.5 D. Z-Score < -2.5 2. What is the drug of choice for treatment of osteoporosis? A. Bisphosphonate B. Teriparatide C. Calcitonin D. All of the Above 9
Post-Assessment Questions 3. Based on recent studies, how much elemental calcium does a postmenopausal woman, who is getting 750mg of dietary calcium need? A. None B. 250mg C. 450mg D. 1200mg Continuing Pharmacy Education Go to www.gotocei.org click on My Portfolio Scroll down to Take Exam Enter Access Code: (case sensitive) Pharmacists - Technicians - 10
2012 Educational Expo Management of Osteoporosis in Postmenopausal Women Ann Philbrick, PharmD, BCPS Post Assessment Questions 1. Which of the following defines osteoporosis? A. T Score 1 to 2.5 B. T Score < 2.5 C. Z Score 1 to 2.5 D. Z Score < 2.5 2. What is the drug of choice for treatment of osteoporosis? A. Bisphosphonate B. Teriparatide C. Calcitonin D. All of the Above 3. Based on recent studies, how much elemental calcium does a postmenopausal woman, who is getting 750mg of dietary calcium need? A. None B. 250mg C. 450mg D. 1200mg
New Evidence-Based Clinical Practice Guidelines: Management of Osteoporosis in Post-Menopausal Women I.D. 65 y.o. postmenopausal caucasian woman PMHx: hypertension and asthma. Meds: metoprolol, aspirin, fluticasone and albuterol inhalers SHX: Retired. Married. Tobacco: none. Alcohol: 1 glass of wine daily. Exercise: rides bicycle 4 days per week. ROS : chronic, mild back pain over past 2 years. Vitals: Ht: 66 inches (168 cm) Wt: 150 lbs (68.2 kg) BP 138/60 Family Hx: mom had hip fracture at age 72 Fracture Hx: patient slipped on the ice and fracture wrist 2 years ago. T-score at left femoral neck: -2.0 FRAX Score Major Osteoporotic: 32% Hip Fracture: 4.3% Estimated dietary calcium intake: 750mg (Assessment) Patient problems: System problems: Intervention: (Plan)